Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Kelambakkam, Tamil Nadu, 603 103, India.
Department of Nutrition, Faculty of Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
Arch Immunol Ther Exp (Warsz). 2023 Feb 20;71(1):6. doi: 10.1007/s00005-023-00669-w.
Colon cancer etiology involves a wide spectrum of genetic and epigenetic alterations, finding it challenging to find effective therapeutic strategies. Quercetin exhibits potent anti-proliferative/apoptotic properties. In the present study, we aimed to elucidate the anti-cancer and anti-aging effect of quercetin in colon cancer cell lines. The anti-proliferative effect of quercetin was assessed in vitro by CCK-8 in normal and colon cancer cell lines. To check the anti-aging potential of quercetin, collagenase, elastase, and hyaluronidase inhibitory activity assays were performed. The epigenetic and DNA damage assays were performed using the human NAD-dependent deacetylase Sirtuin-6, proteasome 20S, Klotho, Cytochrome-C, and telomerase ELISA kits. Furthermore, the aging-associated miRNA expression profiling was performed on colon cancer cells. The treatment with quercetin inhibited cell proliferation of colon cancer cells in a dose-dependent manner. Quercetin arrested colon cancer cell growth by modulating expression of aging proteins including Sirtuin-6 and Klotho and also by inhibiting telomerase activity to restrict the telomere length which is evident from qPCR analysis. Quercetin also exhibited DNA damage protection by reducing proteasome 20S levels. The miRNA expression profiling results displayed differential expression of miRNA in colon cancer cell, and in addition, the highly upregulated miRNA was involved in the regulation of cell cycle, proliferation, and transcription. Our data suggest that quercetin treatment inhibited cell proliferation in colon cancer cells through regulating the anti-aging protein expression and provides better understanding for quercetin's potential use in colon cancer treatment.
结肠癌的发病机制涉及广泛的遗传和表观遗传改变，因此寻找有效的治疗策略具有挑战性。槲皮素具有很强的抗增殖/凋亡作用。本研究旨在阐明槲皮素在结肠癌细胞系中的抗癌和抗衰老作用。通过 CCK-8 在正常和结肠癌细胞系中评估了槲皮素的抗增殖作用。为了检查槲皮素的抗衰老潜力，进行了胶原蛋白酶、弹性蛋白酶和透明质酸酶抑制活性测定。使用人 NAD 依赖性去乙酰化酶 Sirtuin-6、蛋白酶体 20S、Klotho、细胞色素-C 和端粒酶 ELISA 试剂盒进行了表观遗传和 DNA 损伤测定。此外，还对结肠癌细胞进行了与衰老相关的 miRNA 表达谱分析。槲皮素处理以剂量依赖的方式抑制结肠癌细胞的增殖。槲皮素通过调节 Sirtuin-6 和 Klotho 等衰老蛋白的表达，并通过抑制端粒酶活性来限制端粒长度（从 qPCR 分析中可以看出）来阻止结肠癌细胞生长。槲皮素还通过降低蛋白酶体 20S 水平来显示出对 DNA 损伤的保护作用。miRNA 表达谱分析结果显示，结肠癌细胞中 miRNA 的表达存在差异，此外，高度上调的 miRNA 参与了细胞周期、增殖和转录的调节。我们的数据表明，槲皮素通过调节抗衰老蛋白的表达抑制了结肠癌细胞的增殖，为槲皮素在结肠癌治疗中的潜在应用提供了更好的理解。
